The usual trade in this class is that the drug taking off more weight is the harder one to stay on. This chart review found the opposite on both counts [1]. Tirzepatide patients lost more and reported fewer gastrointestinal side effects — 16.6% against 13.4%, and 28.5% against 50.7%.
The response-rate figures follow the same direction. At least 15% of body weight was lost by 56.8% of tirzepatide patients against 40.7% on semaglutide, and at least 20% by 39.0% against 22.1%. Among patients without diabetes the gap widened, to 18.5% against 14.2% — a spread wider than the one in what ordinary care usually delivers.
The prior-medication finding is the most practically useful part. Patients who had used an obesity medication before did worse on both drugs, but the penalty was uneven: semaglutide fell from 14.4% to 10.4%, a loss of four points, while tirzepatide fell from 17.1% to 16.1%, a loss of one. If that holds up, it means treatment history should inform which drug comes next, which is not how prescribing currently works.
Two limits. This was not randomized — who received which drug was a clinical decision shaped by insurance, availability and preference during a period of well-documented shortages, and those forces do not distribute patients evenly. And the cohort was 91.8% White and 74.8% female with a mean BMI of 40.0, which the authors flag themselves in calling for studies in more diverse populations. That is the representativeness question this site raised in who actually gets into trials.
Read against the randomized evidence, the weight ordering here is unsurprising and the tolerability ordering is the interesting claim, because it runs against the network meta-analysis pattern in the drugs that lose most and are tolerated worst. One retrospective cohort does not overturn that. It does say the trade is not automatic.